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Abstract Background Systemic sclerosis (SSc), with unclear pathophysiology, is a paradigmatic rheumatic disease of immunity dysfunction-driven multi-organ inflammation and ultimate fibrosis. Pathogenesis breakthroughs are urgently needed for available treatments halting its unremitting stiffness. This study aims to investigate whether ferroptosis can regulate the progressive SSc fibrosis. Methods In vivo, bleomycin (BLM)-induced mice model was subjected to ferroptosis detection using western blotting, malondialdehyde (MDA), and glutathione (GSH) assays. Pharmacological inhibitor of the acyl-CoA synthetase long-chain family member 4 (ACSL4) was utilized to explore its potential therapeutic effects for fibrosis, from histological, biochemical, and molecular analyses. In vitro, bone marrow-derived macrophages (BMDM) were activated into inflammatory phenotype and then the relationship was evaluated between activation level and ferroptosis sensitivity in lipopolysaccharide (LPS) incubation with gradient concentrations. The potential calpain/ACSL4 axis was analyzed after calpain knockdown or over-expression in Raw264.7. Results Both skin and lung tissue ferroptosis were present in SSc mice with enhanced ACSL4 expression, while ACSL4 inhibition effectively halted fibrosis progressing and provides protection from inflammatory milieu. Meanwhile, a positive regulation relationship between LPS-induced macrophage activity and ferroptosis sensitivity can be observed. After calpain knockdown, both inflammatory macrophage ferroptosis sensitivity and ACSL4 expression decreased, while its over-expression renders ACSL4-envoking condition. Also, calpain pharmacological inhibition reduced both ferroptosis and fibrosis aptitude in mice. Conclusions ACSL4 induces inflammatory macrophage ferroptosis to aggravate fibrosis progressing. ACSL4 and its upregulators of calpains may be potential therapeutic targets for BLM model of SSc.

Background: Triglyceride glycemic (TyG) index is a novel tool for assessing insulin resistance (IR). Recently, TyG index as a potential biomarker f or gestational diabetes mellitus (GDM) has been studied, but its performance is yet inc onclusive. Thus, we performed this systemic review and meta-analysis to evaluate th e performance of TyG index in predicting GDM. Methods: Studies published before March 1, 2021, with comparison of TyG index between GDM patients and healthy controls were retrieved from multiple databases (PubMed, Web of Science, The Cochrane Library, and Embase). The mean diff erence (MD) of TyG index in GDM patients and healthy controls was pooled using ran dom-effect models. Results: Differentiation of TyG index between patients with GDM and cont rols showed significant results. Overall, there is a four-fold increase in T yG index in GDM patients compared with controls (MD: 0.22, 95% CI: 0.07–0.36, P = 0.003; I2 = 71%, P = 0.009). In subgroup analyses according to gestational time, TyG index in t he second trimester predicted GDM with low heterogeneity (MD: 0.26, 95% CI: 0.15–0. 37, P < 0.001; I2 = 0%, P = 0.54), while no such correlation was found in the first trimest er. Conclusion: TyG index, especially in the second trimester, could be a prom ising biomarker for predicting GDM.

When synthesizing a gene with a long DNA sequence, it is usually necessary to divide it into several fragments. Based on these fragments, a set of oligonucleotides for gene assembly is produced. Each oligonucleotide is synthesized separately by the chemical reaction, and then the obtained oligonucleotides are assembled into the full gene sequence, in a specific environment, by polymerase chain reaction (PCR) or ligase chain reaction (LCR). In this paper, an effective and efficient algorithm to divide long genes into oligonucleotide sets is presented. First, according to the length of the overlapping oligonucleotide region, the long DNA sequence to be synthesized is divided into fragments of approximately equal length. Second, the length of these fragments is iterated to dynamically optimize the length of the overlapping regions to reduce melting temperature fluctuations. Then, the improved depth-first search algorithm is used according to the design principle of pruning optimization to obtain a uniform set of oligonucleotides with very close melting temperatures. This will decrease the errors in gene assembly with PCR or LCR. Lastly, the oligonucleotides that have homologous melting temperatures needed for PCR-based synthesis and two-step assembly of the target gene are deduced and outputted.

Supercapacitors have been extensively studied due to their advantages of fast-charging and discharging, high-power density, long-cycling life, low cost, etc. Exploring novel nanomaterial schemes for high-performance electrode materials is of great significance. Herein, a strategy to combine vertical graphene (VG) with MoO3 nanosheets to form a composite VG/MoO3 nanostructure is proposed. VGs as transition layers supply rich active sites for the growth of MoO3 nanosheets with increasing specific surface areas. The VG transition layer further improves the electric contact and adhesion of the MoO3 electrode, simultaneously stabilizing its volume and crystal structure during repeated redox reactions. Thus, the prepared VG/MoO3 nanosheets have been demonstrated to exhibit excellent electrochemical properties, such as high reversible capacitance, better cycling performance, and high-rate capability.

Abstract Molecular structure-editing through nitrogen insertion offers more efficient and ingenious pathways for the synthesis of nitrogen-containing compounds, which could benefit the development of synthetic chemistry, pharmaceutical research, and materials science. Substituted amines, especially nitrogen-containing alkyl heterocyclic compounds, are widely found in nature products and drugs. Generally, accessing these compounds requires multiple steps, which could result in low efficiency. In this work, a molecular editing strategy is used to realize the synthesis of nitrogen-containing compounds using aryl alkanes as starting materials. Using derivatives of O-tosylhydroxylamine as the nitrogen source, this method enables precise nitrogen insertion into the Csp 2-Csp 3 bond of aryl alkanes. Notably, further synthetic applications demonstrate that this method could be used to prepare bioactive molecules with good efficiency and modify the molecular skeleton of drugs. Furthermore, a plausible reaction mechanism involving the transformation of carbocation and imine intermediates has been proposed based on the results of control experiments.

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead compounds optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, “the most fruitful basis for the discovery of a new drug is to start with an old drug”1. Late-stage modification or functionalization of drugs, natural products and bioactive compounds have garnered significant interest due to its ability to introduce diverse elements into bioactive compounds promptly. Such modifications alter the chemical space and physiochemical properties of these compounds, ultimately influencing their potency and druggability. To enrich a toolbox of chemical modification methods for drug discovery, this review focuses on the incorporation of halogen, oxygen, and nitrogen—the ubiquitous elements in pharmacophore components of the marketed drugs—through late-stage modification in recent two decades, and discusses the state and challenges faced in these fields. We also emphasize that increasing cooperation between chemists and pharmacists may be conducive to the rapid discovery of new activities of the functionalized molecules. Ultimately, we hope this review would serve as a valuable resource, facilitating the application of late-stage modification in the construction of novel molecules and inspiring innovative concepts for designing and building new drugs.